tbuckley/cabot-search huggingface dataset:
Variables associated with joint involvement and development of a prediction rule for arthritis in patients with psoriasis. An analysis of the Italian PsoReal database
Authors: Kristine Heidemeyer, Simone Cazzaniga, Letizia Dondi, Giulia Ronconi, Antonella Pedrini, Andrea Bellatreccia, Yichen Zhong, Nello Martini, Luigi Naldi
Journal: Journal of the American Academy of Dermatology (2023)
Immunoglobulin repertoire restriction characterizes the serological responses of patients with predominantly antibody deficiency
Authors: Alexander Troelnikov, Bridie Armour, Trishni Putty, Anupriya Aggarwal, Anouschka Akerman, Vanessa Milogiannakis, Tim Chataway, Jovanka King, Stuart G. Turville, Tom P. Gordon, Jing Jing Wang
Journal: Journal of Allergy and Clinical Immunology (2023)
Killian Jamieson Diverticulum: A Rare Presentation With Food Impaction
Authors: Shubham Sood, Amrit K. Kamboj, Nayantara Coelho-Prabhu
Journal: Clinical Gastroenterology and Hepatology (2023)

A 40-year-old man with heartburn well-controlled on daily omeprazole and without prior dysphagia presented to the emergency department with food impaction. An urgent esophagogastroduodenoscopy was performed. The upper esophageal sphincter extended from 15 to 17 cm. A non-bleeding Killian-Jamieson (KJ) diverticulum with a large opening was found in the proximal esophagus extending from 18 to 20 cm (Supplementary Video). This diverticulum contained a large amount of food (Figure 1A, arrow), which was carefully removed using rat tooth forceps and soft cap. After food bolus removal, the diverticulum was inspected (Figure 1B, green triangle), and the underlying mucosa demonstrated mild stasis changes. Contrast was injected, and fluoroscopy confirmed the KJ diverticulum (Figure 1C, arrow). Esophageal diverticula are a rare but well-established cause of dysphagia and food impaction. It is important to be vigilant for this finding because the obstruction is not intraluminal but instead off to the side and proximal, leading to missed diagnoses. Unlike Zenker’s diverticula, which are located above the cricopharyngeus muscle and posteriorly, KJ diverticula are located below the cricopharyngeus and anterolaterally. Although asymptomatic patients with KJ diverticulum can be managed with close outpatient follow-up, those with symptoms may require surgical or endoscopic intervention. During treatment, identification and avoidance of the recurrent laryngeal nerve is critical given its close proximity to the KJ diverticulum. Our patient underwent outpatient open surgical diverticulectomy without complication and reported no recurrence of symptoms at 6-week follow-up. eyJraWQiOiI4ZjUxYWNhY2IzYjhiNjNlNzFlYmIzYWFmYTU5NmZmYyIsImFsZyI6IlJTMjU2In0.eyJzdWIiOiJhNTA3NjQxZjYxODVkNmY2YmZhYzE4Mjk0NjMxZjkwZCIsImtpZCI6IjhmNTFhY2FjYjNiOGI2M2U3MWViYjNhYWZhNTk2ZmZjIiwiZXhwIjoxNjk0ODM5NzEyfQ.JmF5AGWfPACPOAgB9lW3oCsl2szkI9O-ORHmsIhf7mzEIJ66SBlF6IS6nQfZStxudqjTCpo7sjA1TK4sSBtT36ve4HAMfzOC495tQ9qMwVe0msIZl8xQ1xlCEtufYAXCfkdRKxuc31Hog_TFfLFNIyTeQj9juQU-9BS5-_E8SsAOx49oH9gQk9Dzb9SyVKA7vvgWrlsP571cRoWgW_xiUkcUVMLuyDEQjxt3S7yCNIWJmajHs6ytYLLKUdshdMMSeKBJbYbkM8lQqMnpxLa-T6_6xNr-ShpUpRJwR4Gksj5q44KvYIR6fVV4oy8-ooZwUW9otRBtStx-_I6_RgYz9A Download .mp4 (8.47 MB) Help with .mp4 files Supplementary VideoEGD for dysphagia symptoms.
Peripheral origin exosomal microRNAs aggravate glymphatic system dysfunction in diabetic cognitive impairment
Authors: Lin Zhang, Dongna Li, Pengrong Yi, Jiangwei Shi, Mengqing Guo, Qingsheng Yin, Dingbin Liu, Pengwei Zhuang, Yanjun Zhang
Journal: Acta Pharmaceutica Sinica B (2023)

Cognitive dysfunction is one of the common central nervous systems (CNS) complications of diabetes mellitus, which seriously affects the quality of life of patients and results in a huge economic burden. The glymphatic system dysfunction mediated by aquaporin-4 (AQP4) loss or redistribution in perivascular astrocyte endfeet plays a crucial role in diabetes-induced cognitive impairment (DCI). However, the mechanism of AQP4 loss or redistribution in the diabetic states remains unclear. Accumulating evidence suggests that peripheral insulin resistance target tissues and CNS communication affect brain homeostasis and that exosomal miRNAs are key mediators. Glucose and lipid metabolism disorder is an important pathological feature of diabetes mellitus, and skeletal muscle, liver and adipose tissue are the key target insulin resistance organs. In this review, the changes in exosomal miRNAs induced by peripheral metabolism disorders in diabetes mellitus were systematically reviewed. We focused on exosomal miRNAs that could induce low AQP4 expression and redistribution in perivascular astrocyte endfeet, which could provide an interorgan communication pathway to illustrate the pathogenesis of DCI. Furthermore, the mechanisms of exosome secretion from peripheral insulin resistance target tissue and absorption to the CNS were summarized, which will be beneficial for proposing novel and feasible strategies to optimize DCI prevention and/or treatment in diabetic patients.
Radiology report generation with a learned knowledge base and multi-modal alignment
Authors: Shuxin Yang, Xian Wu, Shen Ge, Zhuozhao Zheng, S. Kevin Zhou, Li Xiao
Journal: Medical Image Analysis (2023)

In clinics, a radiology report is crucial for guiding a patient’s treatment. However, writing radiology reports is a heavy burden for radiologists. To this end, we present an automatic, multi-modal approach for report generation from a chest x-ray. Our approach, motivated by the observation that the descriptions in radiology reports are highly correlated with specific information of the x-ray images, features two distinct modules: (i) Learned knowledge base: To absorb the knowledge embedded in the radiology reports, we build a knowledge base that can automatically distill and restore medical knowledge from textual embedding without manual labor; (ii) Multi-modal alignment: to promote the semantic alignment among reports, disease labels, and images, we explicitly utilize textual embedding to guide the learning of the visual feature space. We evaluate the performance of the proposed model using metrics from both natural language generation and clinic efficacy on the public IU-Xray and MIMIC-CXR datasets. Our ablation study shows that each module contributes to improving the quality of generated reports. Furthermore, the assistance of both modules, our approach outperforms state-of-the-art methods over almost all the metrics. Code is available at https://github.com/LX-doctorAI1/M2KT.
Neoadjuvant radiochemotherapy and perioperative chemotherapy do not represent a standard at the same priority level for esophageal adenocarcinomas (with regard to ‘Oesophageal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up’)
Authors: F. Cellini, S. Manfrida, M.A. Gambacorta, V. Valentini
Journal: Annals of Oncology (2023)
Excess body weight: Novel insights into its roles in obesity comorbidities
Authors: Xiang Zhang, Suki Ha, Harry Cheuk-Hay Lau, Jun Yu
Journal: Seminars in Cancer Biology (2023)

Excess body weight is a global health problem due to sedentary lifestyle and unhealthy diet, affecting 2 billion population worldwide. Obesity is a major risk factor for metabolic diseases. Notably, the metabolic risk of obesity largely depends on body weight distribution, of which visceral adipose tissues but not subcutaneous fats are closely associated with obesity comorbidities, including type 2 diabetes, non-alcoholic fatty liver disease, cardiovascular disease and certain types of cancer. Latest multi-omics and mechanistical studies reported the crucial involvement of genetic and epigenetic alterations, adipokines dysregulation, immunity changes, imbalance of white and brown adipose tissues, and gut microbial dysbiosis in mediating the pathogenic association between visceral adipose tissues and comorbidities. In this review, we explore the epidemiology of excess body weight and the up-to-date mechanism of how excess body weight and obesity lead to chronic complications. We also examine the utilization of visceral fat measurement as an accurate clinical parameter for risk assessment in healthy individuals and clinical outcome prediction in obese subjects. In addition, current approaches for the prevention and treatment of excess body weight and its related metabolic comorbidities are further discussed.
CRISPR-Cas-mediated transcriptional modulation: The therapeutic promises of CRISPRa and CRISPRi
Authors: Louise Bendixen, Trine I. Jensen, Rasmus O. Bak
Journal: Molecular Therapy (2023)

The CRISPR-Cas system is commonly known for its ability to cleave DNA in a programmable manner, which has democratized gene editing and facilitated recent breakthroughs in gene therapy. However, newer iterations of the technology using nuclease-disabled Cas enzymes have spurred a variety of different types of genetic engineering platforms such as transcriptional modulation using the CRISPR activation (CRISPRa) and CRISPR interference (CRISPRi) systems. This review introduces the creation of these programmable transcriptional modulators, various methods of delivery utilized for these systems, and recent technological developments. CRISPRa and CRISPRi have also been implemented in genetic screens for interrogating gene function and discovering genes involved in various biological pathways. We describe recent compelling examples of how these tools have become powerful means to unravel genetic networks and uncovering important information about devastating diseases. Finally, we provide an overview of preclinical studies in which transcriptional modulation has been used therapeutically, and we discuss potential future directions of these novel modalities.
Individualized Treatment Effects: Machine Learning Can Revolutionize Observations, but Let’s Understand What We Are Observing
Authors: Jarrod M. Mosier
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Individualized Treatment Effects: Machine Learning Can Revolutionalize Observations, but Let’s Understand What We Are Observing." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Cystic Fibrosis Reprograms Airway Epithelial IL-33 Release and Licenses IL-33–Dependent Inflammation
Authors: Daniel P. Cook, Christopher M. Thomas, Ashley Y. Wu, Mark Rusznak, Jian Zhang, Weisong Zhou, Jacqueline-Yvonne Cephus, Katherine N. Gibson-Corley, Vasiliy V. Polosukhin, Allison E. Norlander, Dawn C. Newcomb, David A. Stoltz, R. Stokes Peebles
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

Type 2 inflammation has been described in people with cystic fibrosis (CF). Whether loss of CFTR (cystic fibrosis transmembrane conductance regulator) function contributes directly to a type 2 inflammatory response has not been fully defined.
Targeting biased signaling by PAR1: Function and molecular mechanism of parmodulins
Authors: Georg Künze, Berend Isermann
Journal: Blood (2023)

The G protein-coupled receptor (GPCR) protease activated receptor 1 (PAR1) is a therapeutic target that was originally pursued with the aim of restricting platelet activation and the burden of cardiovascular disease. In clinical studies the use of orthosteric PAR1 inhibitors was associated with an increased risk of hemorrhage, including intracranial hemorrhage. As (i) PAR1 is expressed by various cell types, including endothelial cells, (ii) conveys in mice a physiological indispensable function for vascular development during embryogenesis, and (iii) is subject to biased signaling dependent on the activating proteases, orthosteric PAR1 inhibition may be associated with unwanted side effects. Alternatively, the protease activated protein C (aPC) and its variants can promote valuable anti-inflammatory signaling via PAR1. Most recently, small molecule biased allosteric modulators of PAR1 signaling, so called parmodulins, have been developed. Parmodulins inhibit coagulation and platelet activation, yet maintain cytoprotective effects typically provoked by PAR1 signaling upon activation by aPC. Here we review the discovery of parmodulins and their preclinical data, summarize the current knowledge about their mode of action, and compare the structural interaction of parmodulin - PAR1 with that of other intracellularly binding allosteric GPCR modulators. Thus, we highlight the pharmaceutical potential and challenges associated with the future development of parmodulins.
The Clinical Picture of the ERCC6L2 Disease - from Bone Marrow Failure to Acute Leukemia
Authors: Marja Hakkarainen, Ilse Kaaja, Suvi P. M. Douglas, Thomas J Vulliamy, Inderjeet Dokal, Jean Soulier, Lise Larcher, Régis Peffault de Latour, Thierry M Leblanc, Flore Sicre de Fontbrune, Timo Siitonen, Olli Lohi, Eva Hellström-Lindberg, Gisela Barbany, Bianca Tesi, Akiko Shimamura, Fabian Beier, Sharon Rosalie Jackson, Amir Kuperman, Tzipora C. Falik Zaccai, Hannah Tamary, Cristina Mecucci, Ilaria Capolsini, Kirsi Jahnukainen, Urpu Salmenniemi, Riitta Niinimäki, Teppo Varilo, Outi Kilpivaara, Ulla Wartiovaara-Kautto
Journal: Blood (2023)

Biallelic germline ERCC6L2 variants strongly predispose to bone marrow failure (BMF) and myeloid malignancies characterized by somatic TP53-mutated clones and erythroid predominance. We present a series of 52 subjects (35 families) with ERCC6L2 biallelic germline variants collected retrospectively in 11 centers globally, including follow-up of 1165 person-years. At initial investigations, 32 individuals were diagnosed with BMF and 15 with a hematological malignancy (HM). Subjects presented with 19 different variants across ERCC6L2, and we identified a founder mutation c.1424delT in the Finnish patients. The median age of subjects at baseline was 18 years (range 2-65). Changes in complete blood count (CBC) were mild despite severe bone marrow hypoplasia and somatic TP53 mutations, with no significant difference between subjects with or without (HM). Signs of a progressive disease were increasing TP53 variant allele frequency, dysplasia in megakaryocytes and/or erythroid lineage, and erythroid predominance in bone marrow morphology. The median age at onset of HM was 37.0 years (95% CI: 31.5-42.5; range 12-65). Overall survival (OS) at 3 years was 95% (95% CI: 85-100) and 19% (95% CI: 0-39) for patients with BMF and HM, respectively. Patients with myelodysplastic syndrome or acute myeloid leukemia with mutated TP53 undergoing hematopoietic stem cell transplantation had a poor outcome: 3-year OS is 28% (95% CI: 0-61). Our results demonstrate the importance of early recognition and active surveillance of patients with biallelic germline ERCC6L2 variants.
Macrophage metabolic rewiring improves heme-suppressed efferocytosis and tissue damage in sickle cell disease
Authors: Richa Sharma, Ada Antypiuk, S. Zebulon Vance, Deepa Manwani, Quentinn Pearce, James Eric Cox, Xiuli An, Karina Yazdanbakhsh, Francesca Vinchi
Journal: Blood (2023)
DOCK11 deficiency in patients with X-linked actinopathy and autoimmunity
Authors: Charlotte Boussard, Laure Delage, Tania Gajardo, Alexandre Kauskot, Maxime Batignes, Nicolas Goudin, Marie-Claude Stolzenberg, Camille Brunaud, Patricia Panikulam, Quentin Riller, Maryse Moya-Nilges, Jean Solarz, Christelle Reperant, Béatrice Durel, Jean-Claude Bordet, Olivier Pellé, Corinne Lebreton, Aude Magerus-Chatinet, Vithura Pirabakaran, Pablo Vargas, Sébastien Dupichaud, Marie Jeanpierre, Angélique Vinit, Mohammed Zarhrate, Cécile Masson, Nathalie Aladjidi, Peter D Arkwright, Brigitte Bader-Meunier, Sandrine Baron Joly, Joy Benadiba, Elise Bernard, Dominique Berrebi, Christine Bodemer, Martin Castelle, Fabienne Charbit-Henrion, Marwa Chbihi, Agathe Debray, Philippe Drabent, Sylvie Fraitag, Miguel Hié, Judith Landman-Parker, Ludovic Lhermitte, Despina Moshous, Pierre Rohrlich, Frank M Ruemmele, Anne Welfringer-Morin, Maud Tusseau, Alexandre Belot, Nadine Cerf-Bensussan, Marie Roelens, Capucine Picard, Bénédicte Neven, Alain Fischer, Isabelle Callebaut, Mickaël Mathieu Ménager, Fernando E Sepulveda, Frédéric Adam, Frédéric Rieux-Laucat
Journal: Blood (2023)
Comment on Lee et al. Relation of Change or Substitution of Low- and No-Calorie Sweetened Beverages With Cardiometabolic Outcomes: A Systematic Review and Meta-analysis of Prospective Cohort Studies. Diabetes Care 2022;45:1917–1930
Authors: Amée M. Buziau, Gabriëlla A.M. Blokland, Casper G. Schalkwijk, Jean L.J.M. Scheijen, Pomme I.H.G. Simons, Simone J.P.M. Eussen, Pieter C. Dagnelie, Marleen M.J. van Greevenbroek, Anke Wesselius, Coen D.A. Stehouwer, Martijn C.G.J. Brouwers
Journal: Diabetes Care (2023)
Response to Comment on Lee et al. Relation of Change or Substitution of Low- and No-Calorie Sweetened Beverages With Cardiometabolic Outcomes: A Systematic Review and Meta-analysis of Prospective Cohort Studies. Diabetes Care 2022;45:1917–1930
Authors: Jennifer J. Lee, Tauseef Khan, John L. Sievenpiper
Journal: Diabetes Care (2023)
Should I ask my patient if going private is an option?
Authors: Ingrid Torjesen
Journal: BMJ (2023)

Should I ask my patient if going private is an option?With record NHS waiting lists, Ingrid Torjesen asks if paying privately for treatment is an option doctors should raise with patients Ingrid TorjesenYour health is valuable so worth investing in Richard Pile, a GP in St Albans, says "The NHS is facing unprecedented levels of challenge and nowhere is this more obvious than the time people are having to wait for their care.
Reply to ‘Imbalance of threat and soothing systems in fibromyalgia: rephrasing an established mechanistic model?’
Authors: Ana Margarida Pinto, Rinie Geenen, Tor D. Wager, Mark A. Lumley, Winfried Häuser, Eva Kosek, Jacob N. Ablin, Kirstine Amris, Jaime Branco, Dan Buskila, João Castelhano, Miguel Castelo-Branco, Leslie J. Crofford, Mary-Ann Fitzcharles, Marina López-Solà, Mariana Luís, Tiago Reis Marques, Philip J. Mease, Filipe Palavra, Jamie L. Rhudy, Lucina Q. Uddin, Paula Castilho, Johannes W. G. Jacobs, José A. P. da Silva
Journal: Nature Reviews Rheumatology (2023)
Loss of fatty acid degradation by astrocytic mitochondria triggers neuroinflammation and neurodegeneration
Authors: Yashi Mi, Guoyuan Qi, Francesca Vitali, Yuan Shang, Adam C. Raikes, Tian Wang, Yan Jin, Roberta D. Brinton, Haiwei Gu, Fei Yin
Journal: Nature Metabolism (2023)
Maternal third dose of BNT162b2 mRNA vaccine and risk of infant COVID-19 hospitalization
Authors: Michal Lipschuetz, Joshua Guedalia, Sarah M. Cohen, Yishai Sompolinsky, Galit Shefer, Eli Melul, Zivanit Ergaz-Shaltiel, Debra Goldman-Wohl, Simcha Yagel, Ronit Calderon-Margalit, Ofer Beharier
Journal: Nature Medicine (2023)
Time is running out to resolve the NHS workforce crisis
Authors: Juliet Dobson
Journal: BMJ (2023)

Time is running out to resolve the NHS workforce crisisJuliet Dobson managing editor NHS staff are disheartened.Vacancies are at an all time high, morale is declining, and retention is worsening.A report from the Health Foundation has found that stress levels among UK GPs are higher than for GPs in nine other high income countries, and job satisfaction is lower. 1 The healthcare workforce crisis is a global challenge, but the chronic workforce shortages in the NHS are a result of "consistent policy failure," writes Malinga Ratwatte, a GP registrar in London.
Artificial-intelligence-based molecular classification of diffuse gliomas using rapid, label-free optical imaging
Authors: Todd Hollon, Cheng Jiang, Asadur Chowdury, Mustafa Nasir-Moin, Akhil Kondepudi, Alexander Aabedi, Arjun Adapa, Wajd Al-Holou, Jason Heth, Oren Sagher, Pedro Lowenstein, Maria Castro, Lisa Irina Wadiura, Georg Widhalm, Volker Neuschmelting, David Reinecke, Niklas von Spreckelsen, Mitchel S. Berger, Shawn L. Hervey-Jumper, John G. Golfinos, Matija Snuderl, Sandra Camelo-Piragua, Christian Freudiger, Honglak Lee, Daniel A. Orringer
Journal: Nature Medicine (2023)
Panoramic visual statistics shape retina-wide organization of receptive fields
Authors: Divyansh Gupta, Wiktor Młynarski, Anton Sumser, Olga Symonova, Jan Svatoň, Maximilian Joesch
Journal: Nature Neuroscience (2023)

Abstract Statistics of natural scenes are not uniform—their structure varies dramatically from ground to sky. It remains unknown whether these nonuniformities are reflected in the large-scale organization of the early visual system and what benefits such adaptations would confer. Here, by relying on the efficient coding hypothesis, we predict that changes in the structure of receptive fields across visual space increase the efficiency of sensory coding. Using the mouse ( Mus musculus ) as a model species, we show that receptive fields of retinal ganglion cells change their shape along the dorsoventral retinal axis, with a marked surround asymmetry at the visual horizon, in agreement with our predictions. Our work demonstrates that, according to principles of efficient coding, the panoramic structure of natural scenes is exploited by the retina across space and cell types.
Immunization against Zika by entrapping live virus in a subcutaneous self-adjuvanting hydrogel
Authors: Haibin Hao, Shipo Wu, Jiake Lin, Zitong Zheng, Yuemin Zhou, Ying Zhang, Qiang Guo, Fengchao Tian, Mengsu Zhao, Yi Chen, Xurong Xu, Lihua Hou, Xiaoyu Wang, Ruikang Tang
Journal: Nature Biomedical Engineering (2023)
What is the test for, and isn’t that a lot of blood for a child?
Authors: Audrey Chia
Journal: BMJ (2023)

What is the test for, and isn't that a lot of blood for a child?Audrey Chia shares her experience as a parent supporting her child in giving consent for a test Audrey ChiaIt started with a general itch, and after several hours, my 5 year old child's whole body was swollen and covered in hives.We went to an emergency department near our home in Singapore.She was quickly seen and moved to a paediatric ward where we would spend the night.
Long COVID: clues about causes
Authors: Felicity Liew, Claudia Efstathiou, Peter J.M. Openshaw
Journal: European Respiratory Journal (2023)

Many patients report persistent symptoms after resolution of acute COVID-19, regardless of SARS-CoV-2 variant and even if the initial illness is mild [1, 2]. A multitude of symptoms have been described under the umbrella term 'Long COVID', otherwise known as 'post-COVID syndrome' or 'post-acute sequelae of SARS-CoV-2 (PASC)'; for simplicity we will use the term Long COVID. Symptoms are diverse but include breathlessness, fatigue and brain fog, reported to affect up to 69% of cases [3]. Long COVID can be debilitating, 45.2% of patients requiring a reduced work schedule [4]. The WHO estimates that 17 million people in Europe have experienced Long COVID during the first two years of the pandemic [5]. SARS-CoV-2 variants continue to circulate and the risk of post-acute complications remains; a recent study of 56 003 UK patients found that even after Omicron infection, 4.5% suffered persistent symptoms [6]. It is therefore likely that Long COVID will provide a substantial medical and economic burden for the foreseeable future. There is an urgent need to understand mechanisms of disease and develop effective treatments based on this understanding. FL is supported by an MRC clinical training fellowship [award MR/W000970/1]. CE is funded by NIHR [grant P91258-4]. PJMO is supported by a NIHR Senior Investigator Award [award 201385].